Bone marrow abnormalities on magnetic resonance imaging are associated with type II collagen degradation in knee osteoarthritis: A three‐month longitudinal study

Abstract

Objective. Using radiography to assess the efficacy of a disease-modifying osteoarthritis (OA) drug on joint structure is challenging. Subchondral bone marrow abnormalities determined by magnetic resonance imaging (MRI) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) have recently been shown to be predictors of radiographic progression in patients with knee OA, suggesting that these may represent valuable biomarkers with increased sensitivity compared with findings on radiography. The aims of this investigation were to analyze, in patients with knee OA, whether the values associated with these 2 OA biomarkers can change within 3 months, and to investigate the relationships between bone marrow abnormalities and CTX-II.Methods. Knee MRI scans were obtained in 377 patients with painful knee OA (76% women, mean age 63 years, mean disease duration 6.6 years) at both baseline and 3 months. The femoral and tibial condyles and the patella were divided into 8 sites for the scoring of bone marrow abnormalities. A bone marrow abnormality was defined as an area of increased signal on T2-weighted images of the subchondral bone. All scans were reviewed centrally and scored by a single trained radiologist using a validated 4-point scoring method. Fasting urine and serum samples were also collected from all patients at baseline, month 1, month 2, and month 3, in order to measure the levels of urinary CTX-II and serum CTX-I, a biochemical marker of bone resorption.Results. At baseline, 82% of patients had MRI evidence of bone marrow abnormalities. Bone marrow abnormality scores correlated significantly with CTX-II levels (P < 0.0001). Within 3 months, the bone marrow abnormality score decreased in 37 patients (9.8%), increased in 71 patients (18.8%), and did not change in the majority of patients (71.4%). Patients with baseline urinary CTX-II levels in the highest tertile had a relative risk of 2.4 (95% confidence interval 1.1-5.0) of worsening bone marrow abnormalities at 3 months compared with patients with levels in the lowest tertile, after adjustment for age, sex, and body mass index. In patients who showed a decrease in the bone marrow abnormality score at 3 months, urinary CTX-II levels decreased significantly (mean ؊75 ng/mmole creatinine), whereas levels increased (mean ؉23 ng/mmole creatinine) in patients showing an increase in the bone marrow abnormality score (P ‫؍‬ 0.01 between the 2 groups). No significant association between bone marrow abnormalities and serum CTX-I was observed.Conclusion. In patients with painful knee OA, bone marrow abnormalities on MRI can change within only 3 months in ϳ30% of patients. Reduction in the extent of bone marrow abnormalities is associated with a decrease in cartilage degradation.Osteoarthritis (OA) of the knee frequently affects the elderly population and is characterized by cartilage loss, osteophytes, and subchondral sclerosis and cysts (1). Radiography is currently the only method accepted by regulatory agencies for assessing progress...

Correlation of the development of knee pain with enlarging bone marrow lesions on magnetic resonance imaging

“…Another limitation of our study is that we did not study the resolution of pain, but rather its increase. We have previously reported that BMLs are unlikely to disappear in knees with OA, but rather, BMLs often tend to either increase or appear over time (24,25), and this has been confirmed by other investigators (26). We therefore did not believe that it would be productive to focus on the resolution of pain and its association with the resolution of BMLs, since little such resolution occurs.…”

Cross‐Sectional and Longitudinal Associations Between Serum Levels of High‐Sensitivity C‐Reactive Protein, Knee Bone Marrow Lesions, and Knee Pain in Patients With Knee Osteoarthritis

“…Histologically, BMLs represent multiple abnormalities, including osteonecrosis, trabecular abnormalities, and bone remodeling, but rarely edema (17). BMLs may also be caused by inflammation in reaction to cartilage breakdown products or other factors in intruded synovial fluid (18). However, thus far, whether inflammation is associated with BMLs in OA patients is unclear.…”

The bone marrow lesion in osteoarthritis

“…Following 40 patients with knee OA, Phan et al [17] reported both decreases and increases in BML score (graded from 0 to 3 with 3 as severe) from baseline after one or 2-year follow-up. Evaluating 377 patients with painful knee OA, Garnero et al [22] reported that within 3 months, BML scores (as defined before) decreased in 37 patients and increased in 71. Assessing 182 patients with OA at baseline and at 2-year follow-up, Kornaat et al reported that total size of BML changed in 66% patients, with change in size of individual lesions as 45%, new lesions appeared in 21%, and existing lesions completely disappeared in 10% [23].…”